This invention relates to the method and apparatus for producing sterile water or a sterile aqueous solution for biological and medical uses. More particularly, this invention relates to a method and apparatus for producing sterile aqueous solutions sufficiently low in bacteria and pyrogen concentration to permit their administration directly to a patient.
Prior to the present invention, sterile therapeutic liquid compositions have been stored in a hermetically sealed container, typically a thermoplastic flexible, transparent container. The liquid compositions which are packaged and subsequently administered to the patient include intravaneous solutions, peritoneal dialysis solutions, irrigation solutions of the like which contain amino acids, sugars such as dextrose or glucose or minerals including electrolytes, vitamins or mixtures thereof. Hermetically sealed containers for these liquid compositions having the correct dilution commonly are prepared at a centralized location wherein sterility can be carefully controlled to assure that the therapeutic preparations are sufficiently low in bacteria and pyrogens that they can be administered to a patient safely. However this procedure is expensive since it involves the shipment of large volumes of water to locations of use as well as high storage costs at the location of use. In addition, the shelf life of these preparations is limited, typically 18 months to two years so that if they are not used, they must be discarded and replaced.
In order to overcome these disadvantages inherent in preparing the solutions at a centralized location, it has been proposed to prepare them at the location of use on an as-needed basis.
Conventional water purification systems employing well known technologies such as reverse osmosis, deionization and ultrafiltration are capable of producing chemically and biologically pure water for short periods of time. Generally, when these systems are run continuously they will maintain low levels of bacteria and pyrogens for up to about two weeks. After that time, colonies of biologically active materials such as bacteria, yeast and mold will begin to multiply within the system is unacceptably high amounts leading to biologic contamination of the normally pure water produced by these systems.
Some conventional systems regain their capacity to produce biologically pure water by rinsing of the systems with sanitizing agents such as formalin or chlorine which kill all biologic contaminants. While these sanitizing agents perform their function well, they are highly toxic to humans, are difficult to rinse out of the purification system and may be accidently introduced into the water to be purified thereby increasing the risk to the patient.
Another method for insuring biologic purity of water treated with a membrane filter systems is to treat the water with a second process which insures the removal of all living organisms. One such method is to heat the purified water with a pasteurization process. Another method is to pass the purified water through a filter that is capable of filtering from the water all biologically active material. However, both of these processes require that the initial filtration treatment reduces the bacterial contamination to less than about 50 colony forming units per ml. of water. At these levels of contamination, chemical sanitization agents are still currently required.
It has been proposed in U.S. Pat. No. 3,578,774 to provide a sterile urological irrigating liquid composition by passing the liquid composition continuously through a filter designed for removing bacteria. However, this device requires an on site source of nonpyrogenic liquid. It has also been proposed in U.S. Pat. No. 4,253,457 to prepare such irrigation solutions on site by utilizing a combination of a reverse osmosis unit for removing pyrogens, a deionization unit for removing dissolved solids and a filter for removing bacterial in order to produce pyrogen free, bacteria free solution that can be administered directly to the patient. However, this system is limited since there is no way to determine whether or not the reverse osmosis system has failed during use and there is no means for removing pyrogens from the liquid should the reverse osmosis unit fail. In addition, the system requires chemical sanitization and cleaning; thereby increasing risk to the patient. Neither of the means disclosed in U.S. Pat. Nos. 3,578,774 or 4,253,457 is capable of producing water that meets the USP XX standards for water for injection or for irrigation. Accordingly, it would be desirable to provide a means for producing pyrogen free, bacteria free water on site having improved safety over the system disclosed in U.S. Pat. No. 4,253,457 and which can be utilized repeatedly over extended periods so that a wide variety of sterile liquid compositions can be provided on site.
British Pat. Nos. 1,450,030 and 2,034,584 also disclose means for providing pyrogen free and bacteria free aqueous solution at the site of use of the solutions. However, each of these systems relies upon the use of chemical sterilization such as with formalin to sanatize the equipment and heat sterilization wherein the water used to form the aqueous solution is heated to a temperature, typically 150.degree. C. to 160.degree. C. The use of chemical sanitization is undesirable even though it is an effective means for killing microorganisms because it also introduces harmful impurities into the system which can accidently be administered to the patient. Furthermore, heat sterilization of the water used to form the aqueous solution is undesirable since power requirements are high, the heated water can burn the patient if it is not cooled properly and the heat sterilization of the water can introduce air into the system which can accidently be transmitted to the patient.
Accordingly, it would be desirable to provide a means for producing water which is essentially pyrogen free and free of microorganisms which eliminates the need for chemical sanitization and eliminates the need for heating the water to be used to form the aqueous solution above normal body temperature. Furthermore, it would be desirable to provide such a system which can be used at the site where the aqueous solutions produced are administered to a patient. Furthermore it would be desirable to provide such a system which can be sanitized without the need for chemical sanitization or heat pasteurization of the aqueous solution so that it can be used on site over an extended period of time.